A Formal Synthesis of (±)-Lycorine

Abstract

Since the title compound has been known to be de-2 rivable from ('1-a-A -1ycorene-7-one (g), its alternative synthesis is described briefly.Two recent publicationdr2 concerning the synthesis of (?I-lycorine (11, the maln alkaloid of Lycoris radiata HERB (Amaryllidaceael, have promptedusto communicate our own results up to the present.The ('I-cis-oxocyclohexanecarboxylic acid (21 3 , mp 188-189' (EtOHl, was prepared in an acceptable yleld by six steps4 starting from piperonal.Esterification (MeOH, conc.H2S041 of 2, followed by acetalization, epimerization (KOt-Bu, t-HuOH, reflux, 0.5 hrl and hydrolysis (20%aq.KOH-EtOH, reflux) gave (?l-trans-5,5-ethylenedioxy-2-(3',4'-methylenedioxyphenyl)~y~1ohexaneaboxyli acid (21, mp 208.5-209.iD(MeOH), in overall 92.38 yield.Stereospecific conversion of the carboxyl group into an amino group was performed as follows.The Curtius rearrangement (benzene, reflux) of the acid azide derlved from 3 by the conventional mixed anhydride method (1.ClCOOEt, Et N, acetone:Z. 3NaN -H 0 1 afforded the (tl-trans-cyclohexyl isocyanate (i), mp 88-88.5"(Et20-n-3 2 hexane, 73%), M -d i e q u a t o r i a l disposition of the phenyl and isocyanate groups in 1 -